Estimation of pancreatic IRI output rate and its relation to glucose tolerance in normal anaesthetized dogs

Fischer, Uwe; Hommel, H; Gottschling, Hubert; Heinke, P.; Jutzi, E

doi:10.1007/bf00422394

Cited by 9 publications

(9 citation statements)

References 35 publications

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“…Since glucagon and insulin were infused at their normal physiological site and at rates which maintained their plasma concentrations it was possible, by assuming their extraction had not changed, to estimate the secretion rate of each hormone. In the case of insulin, this was about 400 ,U/kg per min, a value in agreement with earlier work (53,54). Recently Fischer et al (54), by using direct A-V difference measurements in the postabsorptive dog, showed that the basal secretion rate of insulin was 392 AU/kg per min.…”

Section: Resultssupporting

confidence: 87%

“…In the case of insulin, this was about 400 ,U/kg per min, a value in agreement with earlier work (53,54). Recently Fischer et al (54), by using direct A-V difference measurements in the postabsorptive dog, showed that the basal secretion rate of insulin was 392 AU/kg per min. The basal secretion rate of glucagon, on the other hand, has not been as clearly assessed but it would appear from the present study that it is about 1 ng/kg per min in the postabsorptive state.…”

Section: Resultssupporting

confidence: 87%

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The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

Cherrington¹,

Chiasson²,

Liljenquist³

et al. 1976

J. Clin. Invest.

243

100

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A B S T R A C T The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusing somatostatin (1 ug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+6 and 81±8%, respectively. Intraportal infusion of insulin and glucagon at rates of400 ,uU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques.Isolated glucagon deficiency resulted in a 35+5% (P < 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration ofthe plasma glucagon level. Isolated insulin deficiency resulted in a 52+16% (P < 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon.In conclusion, in the anesthetized dog fasted overThis work was presented in part at

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Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 87%

The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

Cherrington¹,

Chiasson²,

Liljenquist³

et al. 1976

J. Clin. Invest.

243

100

View full text Add to dashboard Cite

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“…Comparing our restilts, with the rise in pancreatic blood flow after glucose infusion [1,12], it is observed that both changes are parallel. It may further be noted that the effect of glucose infusion to other organ perfusion rates are not clearly understood at present.…”

Section: Discussionmentioning

confidence: 67%

“…administration of glucose induces a significant increase in pancreatic blood flow [1,12]. This observation suggests that besides the insulinogenic and insulin-secretory effects, glucose may produce some changes secondary to alterations in regional circulation.…”

mentioning

confidence: 98%

Hepatic blood flow during rapid intravenous glucose tolerance test

et al. 1980

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Twenty-nine dogs anesthetized with Na-pentobarbital were laparatomized and liver blood flow was measured by 133Xe clearance method. Fifteen dogs of the experimental group were subjected to rapid i.v. glucose tolerance test whereas 14 animals of the control group were treated identically except for infusion of glucose. It was found that the arterial and the portal venous blood glucose rose significantly during the glucose tolerance test. Liver blood flow in the experimental group was 123.8 ml/100 g L/min after operative procedures. It reached 171.9 ml/100 g L/min at 10 min after infusion of glucose (P < 0.01). At 20, 30, and 40 min of the test it was 145.4 (P < 0.05), 143.4 (P < 0.01), 135.1 (P < 0.05) mg/100 g L/min, respectively. Liver blood flow did not change significantly during the observation period in the control series. It is concluded that glucose loading may produce some metabolic effects secondary to rising liver blood flow in addition to changes induced by its rising concentration.

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“…This factor might well vary, but, corresponding to an average loss of 50% of the insulin reaching the liver via the portal vein [8,16], this factor would be 2.0 for insulin secreted or administered into the splanchnic system. In these experiments, however, F = 1.0 because the insulin was administered peripherally so that there was no primary (hepatic) drain of the whole dose.…”

Section: Discussionmentioning

confidence: 99%

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

et al. 1983

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Summary.The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30-60min. The duration of insulin appearance was dosedependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became < 0.3 mU. kg -~. rain 2. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.Key words: Dog, insulin therapy, mathematical model, soluble insulin, depot insulin, absorption, subcutaneous.Until artificial B cells and transplantation are available for the routine long-term treatment of insulin-dependent diabetes, therapeutic research will concentrate mainly on improving the subcutaneous administration of insulin. One approach to this problem is to determine individual optimal insulin dose profiles by means of glucose-controlled insulin infusions and to transpose them into a pattern of separate subcutaneous injections of a variety of preparations [19]. On the other hand, continuous subcutaneous insulin infusions by means of open loop systems are becoming increasingly popular [13,22,24].For successful use, however, both methods require not only carefully recorded blood glucose curves [21] but also detailed knowledge regarding the kinetics of insulin absorption from the subcutaneous injection depot to the insulin distribution space [1,12]. A large number of detailed studies on the disappearance of insulin from its injection depot and how it can be influenced have been reported [2-6, 17, 18, 20, 23, 25]. Moreover Stevenson et al. [26] reported an approach to quantify the absorbed amount of subcutaneously injected insulin by matching the blood glucose response to a programmed intravenous insulin infusion. For practical purposes, a simple mathematical model based on the analysis of pcripheral insulin concentrations and estimation of the rate at which insulin appears in its distribution system seems suitable for obtaining more detailed information [10]. If an organism devoid of functioning B cells is taken as the experimental subject, the rate of insulin appearance can be calculated for any therapeutic dose.The purpose of this study was to use a model to describe the kinetics of insulin appearance after subcutaneous administration of a variety of insulin preparations. The tests were performed on dogs with experimentally induced diabetes because with these a...

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Estimation of pancreatic IRI output rate and its relation to glucose tolerance in normal anaesthetized dogs

Cited by 9 publications

References 35 publications

The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

Hepatic blood flow during rapid intravenous glucose tolerance test

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model

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